Modeling human neurodegenerative diseases in Drosophila: on a wing and a prayer.

The ability of Drosophila genetics to reveal new insights into human neurodegenerative disease is highlighted not only by mutants in flies that show neuronal cell loss, but also by targeted expression of human disease genes in the fly. Moreover, study of Drosophila homologs of various human disease genes provides new insight into fundamental aspects of protein function. These recent findings confirm the remarkable homology of gene function in flies when compared with humans. With the advent of complete genomic sequencing on the horizon, Drosophila will continue to be an outstanding model system in which to unravel the complexities, causes and treatments for human neural degeneration.

[1]  S. Benzer,et al.  Preventing neurodegeneration in the Drosophila mutant bubblegum. , 1999, Science.

[2]  J. Haines,et al.  Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis , 1993, Nature.

[3]  C. Zuker,et al.  Arrestin function in inactivation of G protein-coupled receptor rhodopsin in vivo. , 1993, Science.

[4]  S. Benzer,et al.  Spongecake and eggroll: two hereditary diseases in Drosophila resemble patterns of human brain degeneration , 1997, Current Biology.

[5]  M. Mutsuddi,et al.  Neural disease: Drosophila degenerates for a good cause , 1998, Current Biology.

[6]  D. Selkoe,et al.  The cell biology of β-amyloid precursor protein and presenilin in Alzheimer's disease , 1998 .

[7]  William J. Ray,et al.  A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain , 1999, Nature.

[8]  E. Meyerowitz,et al.  A genetic analysis of visual system development in Drosophilia melanogaster. , 1978, Developmental biology.

[9]  V. Budnik,et al.  The Drosophila β-Amyloid Precursor Protein Homolog Promotes Synapse Differentiation at the Neuromuscular Junction , 1999, The Journal of Neuroscience.

[10]  Craig Montell,et al.  Defective glia induce neuronal apoptosis in the repo visual system of Drosophila , 1995, Neuron.

[11]  P. Kurada,et al.  Retinal degeneration caused by dominant rhodopsin mutations in Drosophila , 1995, Neuron.

[12]  K. Fischbach,et al.  Survival of photoreceptor neurons in the compound eye of Drosophila depends on connections with the optic ganglia. , 1992, Development.

[13]  Iva Greenwald,et al.  Presenilin is required for activity and nuclear access of Notch in Drosophila , 1999, Nature.

[14]  S. Benzer,et al.  Wolbachia, normally a symbiont of Drosophila, can be virulent, causing degeneration and early death. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Dale E. Bredesen,et al.  Caspase Cleavage of Gene Products Associated with Triplet Expansion Disorders Generates Truncated Fragments Containing the Polyglutamine Tract* , 1998, The Journal of Biological Chemistry.

[16]  H. Steller,et al.  Blocking apoptosis prevents blindness in Drosophila retinal degeneration mutants , 1998, Nature.

[17]  S. Selleck,et al.  The influence of retinal innervation on neurogenesis in the first optic ganglion of drosophila , 1991, Neuron.

[18]  C. Haass,et al.  Human presenilin-1, but not familial Alzheimer's disease (FAD) mutants, facilitate Caenorhabditis elegans Notch signalling independently of proteolytic processing. , 1997, Genes and function.

[19]  David Smith,et al.  Involvement of Caspases in Proteolytic Cleavage of Alzheimer’s Amyloid-β Precursor Protein and Amyloidogenic Aβ Peptide Formation , 1999, Cell.

[20]  D L Price,et al.  Genetic neurodegenerative diseases: the human illness and transgenic models. , 1998, Science.

[21]  H. Thoenen,et al.  Disruption of the CNTF gene results in motor neuron degeneration , 1993, Nature.

[22]  M. E. Power The effect of reduction in numbers of ommatidia upon the brain of Drosophila melanogaster , 1943 .

[23]  H. Paulson,et al.  Protein fate in neurodegenerative proteinopathies: polyglutamine diseases join the (mis)fold. , 1999, American journal of human genetics.

[24]  S. Benzer,et al.  Drosophila drop-dead mutations accelerate the time course of age-related markers. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[25]  C. Zuker,et al.  Defective intracellular transport is the molecular basis of rhodopsin-dependent dominant retinal degeneration. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. Fortini,et al.  Apoptotic Activities of Wild-Type and Alzheimer's Disease-Related Mutant Presenilins in Drosophila melanogaster , 1999, The Journal of cell biology.

[27]  S. Benzer,et al.  The Swiss Cheese Mutant Causes Glial Hyperwrapping and Brain Degeneration in Drosophila , 1997, The Journal of Neuroscience.

[28]  Max F Perutz,et al.  Glutamine repeats and neurodegenerative diseases , 1999, Brain Research Bulletin.

[29]  K. Kinzler,et al.  Lessons from Hereditary Colorectal Cancer , 1996, Cell.

[30]  P. Kurada,et al.  Rab6 Regulation of Rhodopsin Transport inDrosophila * , 1998, The Journal of Biological Chemistry.

[31]  E. Wieschaus,et al.  Regulation of Armadillo by a Drosophila APC Inhibits Neuronal Apoptosis during Retinal Development , 1998, Cell.

[32]  M. Goebl,et al.  Localization of Drosophila retinal degeneration B, a membrane- associated phosphatidylinositol transfer protein , 1993, The Journal of cell biology.

[33]  G. Rubin,et al.  The Drosophila ninaC locus encodes two photoreceptor cell specific proteins with domains homologous to protein kinases and the myosin heavy chain head , 1988, Cell.

[34]  J. O'Tousa,et al.  Drosophila retinal degeneration C (rdgC) encodes a novel serine/threonine protein phosphatase , 1992, Cell.

[35]  B. Minke,et al.  Calcium channel blockers inhibit retinal degeneration in the retinal-degeneration-B mutant of Drosophila. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[36]  C. Zuker,et al.  Lights out: deactivation of the phototransduction cascade. , 1997, Trends in biochemical sciences.

[37]  T. Tully,et al.  Human amyloid precursor protein ameliorates behavioral deficit of flies deleted for appl gene , 1992, Neuron.

[38]  Nancy M Bonini,et al.  Expanded Polyglutamine Protein Forms Nuclear Inclusions and Causes Neural Degeneration in Drosophila , 1998, Cell.

[39]  S. Sebti,et al.  Activated Drosophila Ras1 is selectively suppressed by isoprenyl transferase inhibitors. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[40]  S. Benzer,et al.  From the gene to behavior. , 1971, JAMA.

[41]  Steven Finkbeiner,et al.  Huntingtin Acts in the Nucleus to Induce Apoptosis but Death Does Not Correlate with the Formation of Intranuclear Inclusions , 1998, Cell.

[42]  M. Barinaga Is Apoptosis Key in Alzheimer's Disease? , 1998, Science.

[43]  J. Shioi,et al.  Overexpression in Neurons of Human Presenilin-1 or a Presenilin-1 Familial Alzheimer Disease Mutant Does Not Enhance Apoptosis , 1998, The Journal of Neuroscience.

[44]  S. Zipursky,et al.  Analysis of mutants in chaoptin, a photoreceptor cell-specific glycoprotein in Drosophila, reveals its role in cellular morphogenesis , 1988, Cell.

[45]  A. Elia,et al.  Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons , 1998, Nature Genetics.

[46]  K. Fischbach,et al.  Cell degeneration in the developing optic lobes of the sine oculis and small-optic-lobes mutants of Drosophila melanogaster. , 1984, Developmental biology.

[47]  Max F. Perutz,et al.  Glutamine repeats and neurodegenerative diseases: molecular aspects. , 1999, Trends in biochemical sciences.

[48]  J. Penney,et al.  Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease , 1999, Nature.

[49]  I. Greenwald,et al.  Assessment of normal and mutant human presenilin function in Caenorhabditis elegans. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[50]  Harry T Orr,et al.  Ataxin-1 Nuclear Localization and Aggregation Role in Polyglutamine-Induced Disease in SCA1 Transgenic Mice , 1998, Cell.

[51]  J. O'Tousa,et al.  Rhodopsin activation causes retinal degeneration in drosophila rdgC mutant , 1990, Neuron.

[52]  Iris Salecker,et al.  Polyglutamine-Expanded Human Huntingtin Transgenes Induce Degeneration of Drosophila Photoreceptor Neurons , 1998, Neuron.

[53]  M. Fortini,et al.  Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin mutants , 1999, Nature.